729: Whole Brain Diffusion Tensor Imaging Analysis and Outcomes Following Pediatric Cardiac Arrest

Devine, Danielle; Munjal, Neil; Schmithorst, Vincent J.; Ceschin, Rafael; Meyers, Benjamin; Clark, Robert M.; Kochanek, Patrick M.; Panigrahy, Ashok; Fink, Ericka L.

doi:10.1097/01.ccm.0000728804.84156.c2

Cited by 2 publications

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“…11 Furthermore, biomarkers of blood-based white matter injury are helpful tools after pediatric and adult cardiac arrest. 12,13 Thus, neurofilament light (NfL), a component of the neuronal cytoskeleton providing structural support to axons, [14][15][16] and tau, a microtubule-stabilizing neuroaxial protein that maintains stability of axon microtubules, were also included in this study. 17,18 We conducted a prospective multicenter cohort study (Personalizing Outcomes After Child Cardiac Arrest [POCCA]) to evaluate the association of these 4 brain-specific biomarkers on days 1 to 3 after pediatric cardiac arrest with the composite outcome of death or unfavorable adaptive behavior at 1 year.…”

Section: Introductionmentioning

confidence: 99%

“…The UCH-L1 enzyme, which is located in neurons, normally participates in the degradation of damaged proteins, and GFAP forms intermediate filaments that support the shape and function of astroglia cells . Furthermore, biomarkers of blood-based white matter injury are helpful tools after pediatric and adult cardiac arrest . Thus, neurofilament light (NfL), a component of the neuronal cytoskeleton providing structural support to axons, and tau, a microtubule-stabilizing neuroaxial protein that maintains stability of axon microtubules, were also included in this study …”

Section: Introductionmentioning

confidence: 99%

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Association of Blood-Based Brain Injury Biomarker Concentrations With Outcomes After Pediatric Cardiac Arrest

et al. 2022

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IMPORTANCE Families and clinicians have limited validated tools available to assist in estimating long-term outcomes early after pediatric cardiac arrest. Blood-based brain-specific biomarkers may be helpful tools to aid in outcome assessment. OBJECTIVETo analyze the association of blood-based brain injury biomarker concentrations with outcomes 1 year after pediatric cardiac arrest. DESIGN, SETTING, AND PARTICIPANTSThe Personalizing Outcomes After Child Cardiac Arrest multicenter prospective cohort study was conducted in pediatric intensive care units at 14 academic referral centers in the US between May 16, 2017, and August 19, 2020, with the primary investigators blinded to 1-year outcomes. The study included 120 children aged 48 hours to 17 years who were resuscitated after cardiac arrest, had pre-cardiac arrest Pediatric Cerebral Performance Category scores of 1 to 3 points, and were admitted to an intensive care unit after cardiac arrest. EXPOSURE Cardiac arrest. MAIN OUTCOMES AND MEASURESThe primary outcome was an unfavorable outcome (death or survival with a Vineland Adaptive Behavior Scales, third edition, score of <70 points) at 1 year after cardiac arrest. Glial fibrillary acidic protein (GFAP), ubiquitin carboxyl-terminal esterase L1 (UCH-L1), neurofilament light (NfL), and tau concentrations were measured in blood samples from days 1 to 3 after cardiac arrest. Multivariate logistic regression and area under the receiver operating characteristic curve (AUROC) analyses were performed to examine the association of each biomarker with outcomes on days 1 to 3. RESULTS Among 120 children with primary outcome data available, the median (IQR) age was 1.0 (0-8.5) year; 71 children (59.2%) were male. A total of 5 children (4.2%) were Asian, 19 (15.8%) were Black, 81 (67.5%) were White, and 15 (12.5%) were of unknown race; among 110 children with data on ethnicity, 11 (10.0%) were Hispanic, and 99 (90.0%) were non-Hispanic. Overall, 70 children (58.3%) had a favorable outcome, and 50 children (41.7%) had an unfavorable outcome, including 43 deaths. On days 1 to 3 after cardiac arrest, concentrations of all 4 measured biomarkers were higher in children with an unfavorable vs a favorable outcome at 1 year. After covariate adjustment, NfL

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Association of Blood-Based Brain Injury Biomarker Concentrations With Outcomes After Pediatric Cardiac Arrest

et al. 2022

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“…Under normal conditions, UCH-L1, located in neurons, participates in the degradation of damaged proteins 10 and GFAP forms intermediate filaments that support shape and function of astroglia cells 11 . Furthermore, it was shown that blood-based white matter injury biomarkers may serve as prognostic tools after pediatric and adult cardiac arrest 12, 13 . Thus, neurofilament light (NfL), a component of the neuronal cytoskeleton providing structural support to axons 14-16 and tau, a microtubule-stabilizing neuro-axial protein that maintains stability of axon microtubules, were also included in this study 17, 18 .…”

Section: Introductionmentioning

confidence: 99%

“…. Furthermore, it was shown that blood-based white matter injury biomarkers may serve as prognostic tools after pediatric and adult cardiac arrest 12,13 . Thus, neurofilament light (NfL), a component of the neuronal cytoskeleton providing structural support to axons [14][15][16] and tau, a microtubule-stabilizing neuro-axial protein that maintains stability of axon microtubules, were also included in this study 17, 18 . We evaluated the association and accuracy of these four brain-specific biomarkers on days 1-3 post-pediatric cardiac arrest to predict death or unfavorable adaptive behavior composite outcome at 1 year in a prospective multicenter, observational study.…”

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confidence: 99%

“…After covariate adjustment, NfL concentrations on day 1 (odds ratio 5.9 [95% confidence interval 1.8, 19.2], day 2 (11.9 [3.8, 36.9]), and day 3 (10. . Furthermore, it was shown that blood-based white matter injury biomarkers may serve as prognostic tools after pediatric and adult cardiac arrest 12,13 . Thus, neurofilament light (NfL), a component of the neuronal cytoskeleton providing structural support to axons [14][15][16] and tau, a microtubule-stabilizing neuro-axial protein that maintains stability of axon microtubules, were also included in this study 17,18 .…”

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Blood-Based Brain Injury Biomarkers to Prognosticate Outcome after Pediatric Cardiac Arrest

Fink

Kochanek

Panigrahy

et al. 2022

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Background. Prognostication after cardiac arrest in children is challenging due to a lack of validated methods to evaluate direct brain injury. The objective of this multicenter study was to analyze biomarker accuracy to prognosticate outcome 1 year post-arrest. Methods. Fourteen U.S. centers enrolled 164 children ages 48 h - 17 years with pre-arrest Pediatric Cerebral Performance Category score of 1-3 who were admitted to an intensive care unit after cardiac arrest. Glial fibrillary acidic protein (GFAP), ubiquitin carboxyl-terminal esterase- L1 (UCH-L1), neurofilament light (NfL), and Tau concentrations were measured in blood samples from post-arrest days 1-3 using Quanterix Simoa 4-Plex assay, Billerica, MA. Unfavorable outcome was death or survival with Vineland Adaptive Behavioral Scale-Third Edition score < 70 at 1 year. We analyzed area under receiver operator curve (AUROC) and performed multivariate logistic regressions to determine the association of each biomarker with outcome on days 1-3. Results. Fifty of 120 children with primary outcomes available had an unfavorable outcome, including 43 deaths. Compared to those with favorable outcomes, more children with unfavorable outcome had out-of-hospital (36% vs. 70%) and unwitnessed (7% vs. 46%) events, p<0.05. For days 1-3, concentrations of all four measured biomarkers were increased in children with an unfavorable vs. favorable outcome, p<0.05. On post-arrest day 1, NfL demonstrated the best outcome classification (AUROC 0.731 [95% confidence interval 0.642, 0.820]) while UCH-L1 performed best on days 2 (0.860 [0.785, 0.935]) and 3 (0.837 [0.747, 0.926]). After covariate adjustment, NfL concentrations on day 1 (odds ratio 5.9 [95% confidence interval 1.8, 19.2], day 2 (11.9 [3.8, 36.9]), and day 3 (10.2 [3.1, 33.3]), UCH-L1 on day 2 (11.3 [3.0, 42.4]) and day 3 (7.6 [2.1, 27.1]), GFAP on day 2 (2.3 [1.2, 4.5]) and day 3 (2.2 [1.2, 4.0]), and tau on day 1 (2.4 [1.1, 5.3]), day 2 (2.3 [1.3, 4.0]), and day 3 (2.0 [1.2, 3.6]) were associated with unfavorable outcome, p<0.05. Conclusions. Blood-based brain injury biomarkers accurately prognosticated death or unfavorable adaptive behavior composite outcome at 1 year after pediatric cardiac arrest. Accuracy of biomarkers to predict neurodevelopmental outcomes beyond 1 year should be evaluated.

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729: Whole Brain Diffusion Tensor Imaging Analysis and Outcomes Following Pediatric Cardiac Arrest

Cited by 2 publications

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Association of Blood-Based Brain Injury Biomarker Concentrations With Outcomes After Pediatric Cardiac Arrest

Association of Blood-Based Brain Injury Biomarker Concentrations With Outcomes After Pediatric Cardiac Arrest

Blood-Based Brain Injury Biomarkers to Prognosticate Outcome after Pediatric Cardiac Arrest

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